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Dysregulated ceramides metabolism via PTPN11 exposes a metabolic vulnerability to breast cancer metastasis
Sen Qiao1, Tianwei Wang1, Hongmei Wang2
1Assisted Reproduction Center, Northwest Women's and Children's Hospital, No. 73 Houzaimen, North Street, Xincheng District, Xi'an, 710003, China.
Abstract:
Breast cancer is a prevalent malignant tumor, posing a significant threat to women's health globally due to its increasing incidence and tendency to affect younger patients. Protein tyrosine phosphatases (PTPs) are a class of enzymes that have emerged as potential targets for various tumors, including breast cancer, because they can modulate oncogenic tyrosine kinases, which are both tumor-suppressive and oncogenic. The regulation of tyrosine phosphorylation levels is crucial for cell proliferation and differentiation. Although the clinical biomarker potential of PTPs is not fully explored, there is evidence to suggest that they may serve as clinical biomarkers and therapeutic targets for breast cancer. We found that increased expression levels of PTPN11 and PTPN3 were associated with a higher risk of death in patients with breast cancer, while PTPN11 and PTPN18 are significantly associated with overall survival in patients with estrogen receptor-positive (ER+) breast cancer. Meanwhile, PTPN11 expression was found to be negatively associated with survival in patients with ER+ breast cancer. Furthermore, PTPN11 exposes a metabolic vulnerability to breast cancer metastasis via dysregulated ceramide metabolism. Therefore, we speculate that PTPN11 has the potential to serve as a therapeutic target for breast cancer by regulating lipid metabolism reprogramming.
Insights
Protein tyrosine phosphatases (PTPs) are key in breast cancer. PTPN11 and PTPN3 indicate higher mortality risk, while PTPN11 may be a therapeutic target by altering lipid metabolism.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Breast cancer is a global health threat, particularly affecting younger women.
- Protein tyrosine phosphatases (PTPs) regulate tyrosine phosphorylation, impacting cell processes and cancer development.
- PTPs are potential therapeutic targets and biomarkers in breast cancer due to their role in modulating oncogenic tyrosine kinases.
Purpose of the Study:
- To investigate the role of specific PTPs as clinical biomarkers and therapeutic targets in breast cancer.
- To explore the association between PTP expression levels and patient survival outcomes.
- To examine the potential of PTPN11 as a therapeutic target by investigating its role in metabolic reprogramming and metastasis.
Main Methods:
- Analysis of PTP expression levels in breast cancer patient cohorts.
- Correlation of PTP expression with clinical outcomes, including risk of death and overall survival.
- Investigation of PTPN11's role in ceramide metabolism and its link to breast cancer metastasis.
Main Results:
- Increased PTPN11 and PTPN3 expression correlated with higher mortality risk in breast cancer patients.
- PTPN11 and PTPN18 expression were significantly associated with overall survival in estrogen receptor-positive (ER+) breast cancer.
- PTPN11 expression showed a negative association with survival in ER+ breast cancer patients.
- PTPN11 was found to dysregulate ceramide metabolism, creating a vulnerability for breast cancer metastasis.
Conclusions:
- Specific PTPs, including PTPN11 and PTPN3, show potential as prognostic biomarkers for breast cancer.
- PTPN11 may serve as a therapeutic target for breast cancer, particularly by modulating lipid metabolism to inhibit metastasis.
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